{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T02:14:57Z","timestamp":1787537697446,"version":"build-2736575974"},"reference-count":73,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T00:00:00Z","timestamp":1600992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["5R25G06414\u201016"],"award-info":[{"award-number":["5R25G06414\u201016"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006545","name":"National Institute on Minority Health and Health Disparities","doi-asserted-by":"publisher","award":["2U54MD007590\u201032"],"award-info":[{"award-number":["2U54MD007590\u201032"]}],"id":[{"id":"10.13039\/100006545","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:p>The risk factors for prostate cancer include a high\u2010fat diet and obesity, both of which are associated with an altered cell environment including increased inflammation. It has been shown that chronic inflammation due to a high\u2010fat diet or bacterial infection has the potential to accelerate prostate cancer as well as its precursor, prostatic intraepithelial neoplasia (PIN), development. However, the underlying mechanism of how chronic inflammation promotes prostate cancer development, especially PIN, remains unclear. In this study, we showed that more macrophages were present in PIN areas as compared to the normal areas of human prostate. When co\u2010culturing PIN cells with macrophages in 3D, more PIN cells had nuclear localized cyclin D1, indicating that macrophages enhanced PIN cell proliferation. We identified ICAM\u20101 and CCL2 as chemoattractants expressed by PIN cells to recruit macrophages. Furthermore, we discovered that macrophage\u2010secreted cytokines including C5a, CXCL1, and CCL2 were responsible for increased PIN cell proliferation. These three cytokines activated ERK and JNK signaling in PIN cells through a ligand\u2010receptor interaction. However, only blockade of ERK abolished macrophage cytokines\u2010induced cell proliferation of PIN. Overall, our results provide a mechanistic view on how macrophages activated through chronic inflammation can expedite PIN progression during prostate cancer development. The information from our work can facilitate a comprehensive understanding of prostate cancer development, which is required for improvement of current strategies for prostate cancer therapy.<\/jats:p>","DOI":"10.1111\/febs.15541","type":"journal-article","created":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T11:58:12Z","timestamp":1598875092000},"page":"1871-1886","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Macrophages expedite cell proliferation of prostate intraepithelial neoplasia through their downstream target ERK"],"prefix":"10.1111","volume":"288","author":[{"given":"Mikalah U.","family":"Thomas","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Clark Atlanta University GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin K.","family":"Messex","sequence":"additional","affiliation":[{"name":"Center for Cancer Research and Therapeutic Development Clark Atlanta University GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tu","family":"Dang","sequence":"additional","affiliation":[{"name":"Center for Cancer Research and Therapeutic Development Clark Atlanta University GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarki A.","family":"Abdulkadir","sequence":"additional","affiliation":[{"name":"Department of Urology Northwestern University Chicago IL USA"},{"name":"Department of Pathology Northwestern University Chicago IL USA"},{"name":"Robert H. 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